Clinical and clonal characteristics of monoclonal immunoglobulin M‐associated type I cryoglobulinaemia

• Published in: British journal of haematology Vol. 204; no. 1; pp. 177 - 185
• Main Authors: Khwaja, Jahanzaib, Vos, Josephine M. I., Pluimers, Tessa E., Japzon, Nicole, Patel, Aisha, Salter, Simon, Kwakernaak, Arjan J., Gupta, Rajeev, Rismani, Ali, Kyriakou, Charalampia, Wechalekar, Ashutosh D., D'Sa, Shirley
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2024
• Subjects: Amyloidosis; Antibodies, Monoclonal; Benign monoclonal gammopathy; Cold agglutinin disease; Cryoglobulinemia - etiology; Cryoglobulins; Hematology; Humans; Immunoglobulin M; Immunoglobulins; Lymphoma, B-Cell; Medical treatment; Monoclonal Gammopathy of Undetermined Significance - diagnosis; MyD88 protein; Non-Hodgkin's lymphoma; Paraproteins; Patients; Peripheral neuropathy; Survival; Waldenstrom Macroglobulinemia - pathology; non-Hodgkin lymphoma; MGUS; cryoglobulin; Waldenström macroglobulinaemia; cryoglobulinaemia
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.19112

Monoclonal immunoglobulin M‐associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9‐year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non‐Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM‐associated disorders (including cold agglutinin disease [CAD], anti‐MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p  < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild‐type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin‐related symptoms alone at a median of 38 days (range: 6–239) from cryoglobulin detection. At a median follow‐up of 3 years (range: 0–10), 3‐year cryoglobulinaemia‐treatment‐free survival was 77% (95% CI: 68%–84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia‐related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62–341.36, p  < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13–7.71, p  = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.